The purpose of the Molecular Genetics core is to (1) assay for mutations in SOD1 and other protein antioxidant genes in genomic DNA samples from all patients analyzed in Project 1; (2) prepare constructs suitable for the synthesis of various forms of tetanus C fragment: SOD1 protein for Project 3; and (3) prepare cDNA constructs with all of the known SOD1 mutations to be available potentially for the other projects as needed. This core unit will be operated within the Day Neuromuscular Research Laboratory under the direction of Dr. Robert Brown. Using standard techniques she routinely now employs in the Day Lab, Dr. Betsy Hosler will perform single strand conformational polymorphism analysis, direct sequencing of PCR products amplified from patients' genomic DNA, preparation and cloning of different tetanus C fragment - SOD1 preparations, PCR amplification of patient SOD1 cDNA from lymphoblastoid cell lines and site directed mutagenesis of wild type SOD1. The services provided by this core will be essential both for patient diagnosis and preparation of experimental reagents for three of the four projects.